Large Joints Feature

Indian Scientists Develop Polymer for Bone Implants

Biloine W. Young • Mon, July 18th, 2016

Researchers at the Indian Institute of Science (IISc) in New Delhi, India, report that they have developed a material made of polymer nanocomposite (a polymer having nanoparticles) that can be used in bone implants.

“Age takes a toll on people’s bone health leading to diseases like osteoarthritis, osteonecrosis and rheumatoid arthritis. Rapid advancement in technology has however enabled in treating such diseases by surgical replacement, ” an IISc official said in a release.

To make certain that the material was compatible with human body tissues and did not cause any toxic effects the researchers grew two types of cells—bone cell and stem cells—on the material. Both of these cells showed enhanced proliferation and increased metabolic activity on the polymer nanocomposite. Researchers interpreted this to mean that it was a good material for bone implants.

“This material supports growth of stem cells and bone cells in parallel. It has high wear resistance, better life span, is lightweight and doesn’t cost much to manufacture, ” said Rahul Upadhyay, a research scholar at the Material Research Centre, IISc.

The researchers also tested the mechanical strength and results showed the new material has moderate load bearing capability and was less prone to mechanical damage. “This material could be a promising candidate for moderate load bearing orthopaedic applications. The main aim of our research is to develop a prototype of an acetabular socket for hip implants with dimensions specially suited for Indian patients, ” he said.

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3D Bio-Ink Prints Cartilage and Bone

Biloine W. Young • Fri, July 1st, 2016

Researchers at the University of Bristol School of Cellular and Molecular Medicine have developed a stem cell bio-ink that can produce 3D printed cartilage and bone implants. The new stem cell ink contains two different polymers. One is a natural polymer extracted from seaweed. The second is a synthetic polymer that causes the ink to solidify when temperatures are raised. The seaweed-based material provides the structural support that is deemed necessary to sustain cell nutrients.

The project is directed by Adam Perriman, M.D. who explained that the custom formulation can be extruded by a 3D printer to form complex living 3D architectures, which will start to transform from a liquid into a gel at 37°C. Perriman said, “Designing the new bio-ink was extremely challenging. You need a material that is printable, strong enough to maintain its shape when immersed in nutrients, and that is not harmful to the cells. We managed to do this, but there was a lot of trial and error before we cracked the final formulation.”

Perriman noted that the synthetic material is only temporarily present. “What was really astonishing for us was when the cell nutrients were introduced, the synthetic polymer was completely expelled from the 3D structure, leaving only the stem cells and the natural seaweed polymer. This, in turn, created microscopic pores in the structure, which provided more effective nutrient access for the stem cells, ” he said.

The stem cells present in the bio-ink are purposefully adapted to be used for 3D bioprinted bone and cartilage implants. They achieved this by differentiating the stem cells into osteoblasts and chondrocytes which are cells that secrete bone and cartilage matrixes. Over a period of several weeks, according to Perriman, these materials grow into full-sized cartilage or bone structures that can be implanted.

The research group’s findings have been published in the journal of Advanced Healthcare Materials in a paper entitled “3D Bioprinting Using a Templated Porous Bioink.”

Hydrogels Keep Stem Cells in Place

Biloine W. Young • Tue, June 17th, 2014

Stem cells do not always stay where they are put. When they are used to regenerate tissue, many wind up migrating away from the repair site, which disrupts the healing process. Researchers at the University of Rochester, under the direction of Assistant Professor of Biomedical Engineering Danielle Benoit, Ph.D., have developed a technique that keeps the stem cells in place. The key, as explained in a paper published in Acta Biomateerialia, is to encase the stem cells in polymers that attract water and then disappear when their task is completed.

Benoit explains that this has been used to repair other types of tissue but never before tried on bone. “Our success opens the door for many types of bone repairs. We should be able to pinpoint repairs within the periosteum, or outer membrane of bone material, ” she said.

The polymers used by Benoit and her team are called hydrogels because they hold water, necessary to keep the stem cells alive. The hydrogels are designed to degrade and disappear before the body interprets them as foreign bodies and begins a defense response.

The research team transplanted cells onto the surface of mouse bone grafts and studied the cell behavior both inside and outside the body. They removed all living cells from the donor bone fragments so that tissue regeneration could be accomplished only by the stem cells. They genetically modified the stem cells to include genes that give off fluorescence signals. The bone material was then coated with the hydrogels, which contained the fluorescently labeled stem cells, and planted them into the defect of the damaged mouse bone.

At that point the researchers began monitoring the repair process with longitudinal fluorescence to determine if there would be an appreciable loss of stem cells in the in vivo samples as compared to those in the in vitro environments. They found that there was no measurable difference between the concentrations of stem cells in the various samples. Virtually all of the stem cells stayed in place to complete their work in generating new bone tissue. Benoit believes that, as a result of this research, degradable hydrogels show promise in many research areas as, for example, in tissue regeneration after heart failure.

New Shape-Memory Polymer Molds to Shape of Bone Defect

Elizabeth Hofheinz, M.P.H., M.Ed. • Wed, August 20th, 2014

Blowing autograft out of the water? Perhaps. Researchers from Texas A&M University are reporting that they have developed a new material that expands with warm salt water and “precisely” fill bone defects. The material—a shape-memory polymer (SMP)—is also a scaffold for new bone growth.

“The problem is that the autograft is a rigid material that is very difficult to shape into these irregular defects, " said Melissa Grunlan, Ph.D., leader of the study, in the August 13, 2014 news release. Also, harvesting bone for the autograft can itself create complications at the place where the bone was taken.

The team notes that surgeons may also use bone putty or cement as an option, but that both of these “become very brittle when they harden, and they lack pores, or small holes, that would allow new bone cells to move in and rebuild the damaged tissue.”

As noted in the news release, the researchers “made a porous SMP foam by linking together molecules of poly(ε-caprolactone), an elastic, biodegradable substance that is already used in some medical implants. The resulting material resembled a stiff sponge, with many interconnected pores to allow bone cells to migrate in and grow. Upon heating to 140 degrees Fahrenheit, the SMP becomes very soft and malleable. So, during surgery to repair a bone defect, a surgeon could warm the SMP to that temperature and fill in the defect with the softened material. Then, as the SMP is cooled to body temperature (98.6 degrees Fahrenheit), it would resume its former stiff texture and ‘lock’ into place.”

The SMP, which is biodegradable, was coated with a sticky substance known as polydopamine, which helps lock the polymer into place. The hope is that it will help osteoblasts adhere and spread throughout the polymer. In order to test the SMP’s efficacy regarding bone cell growth, the researchers added human osteoblasts to the polymer. According to the news release, “After three days, the polydopamine-coated SMPs had grown about five times more osteoblasts than those without a coating. Furthermore, the osteoblasts produced more of the two proteins, runX2 and osteopontin, that are critical for new bone formation.”

Srinivas Pentyala, Ph.D. is director of Translational Research at Stony Brook Medical Center in New York. He told OTW, “We used bioinformatics program to discover novel bioactive peptides that can be utilized as lead drug compounds to cure various diseases.”

“One of our virtual peptides, CRFP was found to be osteogenic as well as osteoinductive. As such, CRFP is being considered a lead drug anabolic compound for osteoporosis. As CRFP has also osteogenic properties, we are working on creating biomimetic and biocompatible bone implants where scaffolds made of inert material are seeded with stem cells and treated with CRFP to produce bine matrix, which are currently being tested for implantation.”

The authors wrote, “3D-printed scaffolds based on physiological trabecular bone patterning were printed. MC3T3 cells were cultured on these scaffolds in osteogenic media, with and without the addition of Calcitonin Receptor Fragment Peptide (CRFP) in order to assess bone formation on the surfaces of the scaffolds.”

Dr. Pentyala commented to OTW, “Our lab is the first one to report that osteoblasts can be cultured on 3D printing plastic scaffolds. Also, the scaffolds were designed based on reverse engineering, we procured CT scans of bone cross sections and converted them to STL files using CAD and print the implants. Also, the design of the experiment to seed stem cells and transform them into bone producing cells on artificial scaffolds is unique.”

“Our osteogenic peptide, CRFP is osteogenic as it has multiple properties in fracture healing, bone cell differentiation and bone matrix production. As such CRFP is being used not only as a lead drug compound for osteoporosis but also being tested in fracture healing and creating bone grafts.”

“Reverse engineering to produce biomimetic scaffolds is the key to creating grafts and implants that are biocompatible.

New Hydrogels Hold, Support Stem Cells

Biloine W. Young • Tue, July 15th, 2014

In a first for bone tissue repair, researchers at the University of Rochester, New York, have encased regenerative stem cells in a hydrophilic polymer. This prevented the stem cells from leaving a repair site in the body early and speeded up the healing process, according to Vaun Saxena, writing for Fierce Drug Delivery.

Hydrogels are hydrophilic polymer chains that easily absorb water and are being researched by biotechnologists for their potential drug delivery applications because they exhibit properties similar to human tissue."Our success opens the door for many—and more complicated—types of bone repair, " assistant professor of biomedical engineering Danielle Benoit, Ph.D. said in the university’s news release. "For example, we should now be able to pinpoint repairs within the periosteum—or outer membrane of bone material, " he said.

Currently, according to Benoit, stem cells are injected directly into bone tissue without any protective substance to shield them from the body's immune system, which sees them as foreign agents. By modifying the hydrogels, the researchers successfully controlled the amount of time it took for the polymers to dissolve, allowing for the customization of stem cell behavior based on specific needs and circumstances.

In a related development researchers at Tohoku University in Japan have come up with a stretchable and durable electrode-hydrogel. This hydrogel withstood repeated stretching and sterilization procedures while maintaining electrical conductivity, Asian Scientist magazine reported. The device kept its shape after being repeatedly bent, stretched to twice its length, immersed in water for 6 months and autoclaved for 20 minutes at a time.

In addition to withstanding that abuse, the Tohoku team said that cultures of neural and muscle cells on the hydrogel were able to "adhere, proliferate and differentiate, " which are key to developing bio-integrated wearable devices featuring integrated electronics.

"Our study paves the way for the development of complex electronically responsive and spatially controlled nerve muscle cell co-cultures, opening a new avenue of 'intelligent biorobotics', " the Tohoku team, led by Matsuhiko Nishizawa, wrote in Advanced Healthcare Materials.